SU727655A1 - Method of preparing sodium salts of n-acylphosphatidealethanolamines - Google Patents

Description

(54) METHOD FOR PRODUCING SODIUM SALTS OF K-ACYLPHOSPHATIDALETHANOLAMINES

are reacted with N-acylOxysuccinimide of the general formula - -: 0

/ -

com

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about

-SNz or (CH) SND

where r

in benzene or chloroform at 40-50s in the presence of triethylamine, followed by saponification of the reaction product with a solution of sodium bicarbonate ...

The process is preferably carried out with two equivalents of N-acyloxysuccinimide for 3–4 hours, and it is necessary to mix the intermediate acyl phosphates with an aqueous solution of sodium bicarbonate. The yield of sodium salts of N-acylphosphatidal ethanolamines of formula I was 80-82%. The starting sodium salt of phosphatidalethanolamine is obtained by known methods from natural sources or by chemical synthesis 3.

The structure of the compounds was confirmed by IR, spectroscopy, optical rotation dispersions, thin-layer chromatography on various sorbents, and elemental analysis.

. PRI me R 1. Sodium salt of cis-i-O- (1-hexadecenyl) 2-stearoyl-3p-glycero-3-phospho-H-acetyl ethanolamine (1a).

Mixture, g: sodium salt of cis-1-0- (-hexado-chenyl) -2-stereoyl-Sn-glycero-3-phosphazanolamine 0.22; N-acetoxysuccinimide 0.10 and anhydrous triethylamine D7lO, in 20 ml of anhydrous benzene is stirred for 3 h at 40 s. The benzl is evaporated, the residue is dissolved in 10 ml of 3: 3 methanol, 1: 1, and 2 ml of an aqueous solution is added. NaHCOj (50%), stirred for 2 hours at 40 ° C, the solution is evaporated in vacuo (20 mm), the residue is chromatographed on a column of silica gel L 100/160 (20 g). The substances are eluted with a mixture of chloroformmethanol, 9: 1. The output of 0.17 g (82,4%), so pl. 132-140 ° C, R 0.37 (Silufol UV 254, chloroform-methanol, 4: 1), 0.41 (silica gel L 5/40 /, chloroform-methanol 4: 1) DON (t6l: Wall, -pri ): (COs-eq -0.4, (dL) 435 -2.2, (A) BSA, -5.8, (OO, 2: -10.8. IR spectrum (l), cm): 3350 (LH in NHCOCB), 3020 (-CH-CH-), 1735 (7 C-0 V OCOR), 1665 and 1560 (-7 C-0 in SSTCH), 1250 (P-O), 1180-1040 ( Р-О-С). NMR spectrum (MD): 0.96 (), 1.23 (-CH2, -gl chain), 2.44G (-HCOCH) 3.78 (multiplet, -CHg glycerol), 4.25 (multiplet, -0-CH-CH) 5-85 (doublet, J 6.2 Hz, -O-CH-CH-).

Found,%: P 4.05; N 1.82, 9PNNa.

Calculated,%: P 4, 03; N 1.82,

727655

Example 2. Sodium salt. cis-1-0- (1-hexadecenyl) -2-stearoyl-3p-glycero-3-phospho-N-stearoyl ethanolamine (16). Mixture g: sodium salt of cis-1-0- (1-hexadecenyl) -2-stearoyl-8p-glycero-3-f, osfoethanolamine 0.20 N-stearoylsuccinimide 0.18 and anhydrous triztilamine 0.10 in 20 ml anhydrous benzene was stirred for 4 hours at 50 ° C. The benzene was evaporated, the residue was diluted in 10 ml, chloroform-methanol mixture, 1: 1, and 2 ml of sodium bicarbonate aqueous solution (50%) was added, stirred for 2 hours at 40 ° C. in vacuo (20 mm), the residue is chromatographed on a qel5 column with a lath of L 10p / 1bO (20 g). Substance. zlyuyut mixture with chloroform-methanol, 10: 1. Sss 0.22 g (81.2%), mp. 176180 ° C, Rf 0.51 (Silufol WV 254, chloroform-methanol, 4: 1). ORD (toluene,

0 at (60589+ 1.0 (s) 4g 5 + 13, (+ .2.6 °, (i) + 3.6. IR-spectrum p (1,): 3350 (NH in NHCOR), 3020 ( -CH-CH-), 1735 (C-ov OCOR), 1665 and 1560 (C-0 B NHCOR). 1250 (P-0),

5 1180-1040 (-P-0-C-). PMR spectrum. ; (G, ppm): 0.98 (), 1.25. (CH-Chains) 2.56 (-CHSN2 (CHy CH3), 3.79 (multiplet CH -glycerol,), 4.25 (multiplet, -0-CH-CH-), 5.86

(doublet, J 6.2 Hz, -O-CH-CH-).

Found,%: P 3.12; Nl, 72.

5 OlOePNNa

Calculated,%: P / 3.12, N 1.74. . Thus, the proposed method allows one to chemically obtain N-acylphosphatidalmethanolamines in the form of sodium salts with a yield of 80-82%.

The process is proceeding under mild conditions that allow the preservation of the natural structure (y), using available reagents.

Claims (3)

1. Debuch D., Wendt G. Eine neue Gruppe von colaminhaltige Glycerinphosphatigeh auz Gehizn Z. Physiol. Chem. 19.67 ,. 348, 471-474. : 2. Aneja R. Chadha 3. S., 5 Knaggs. A., N-acylphosphatidilethanolamines, in nature in aud etereochemistry. Biochem. Biophys. Res. Caim. 1969, 36, 3. 0 3. Chebyshev A.V., Serebrennikova G.A. Evstigneeva P.P. Synthesis of primitive, unsaturated phosphatidal ethanchelamines and phosphatidalcholines. Viorgan, Chem., 1977, 3, 10, 13625